Project Summary ? Neuroimaging Core (NIC) The Neuroimaging Core (NIC) of the IADC brings advanced imaging tools in support of the goal of effectively preventing and treating AD by 2025. The NIC has been productive in developing and implementing leading- edge imaging protocols and imaging genetics analysis techniques, collaborating with NIA-funded initiatives (e.g., ADNI, DIAN, ADGC, etc.), and in providing training in neuroimaging and imaging genetics to scientists of all levels (undergraduate to faculty) and disciplines (neuroscience, genetics, computer science, physicians, etc.). In the next funding period the NIC will continue to pursue the following specific aims: (1) Support funded research in the IADC, IU Center for Aging Research, and related programs that currently employ or could benefit from advanced neuroimaging; (2) Provide standardized, state-of-the-art neuroimaging acquisition and analysis protocols; (3) Expand transdisciplinary regional neuroscience research using advanced neuroimaging tools to study disease mechanisms and treatments for neurodegeneration; (4) Support and collaborate with major national and international AD-related research consortia using neuroimaging and genetics methods; (5) Provide transdisciplinary educational opportunities in neuroimaging and genetics of AD and other degenerative disorders for basic and clinical scientists at all levels from undergraduates to post-doctoral fellows and faculty, as well as dissemination of neuroimaging results to the community. The NIC, working closely with the Clinical Core, will perform state-of-the-art advanced multimodal MRI ( Siemens Prisma 3T: high resolution structural and 3D pCASL perfusion, multiband resting-state and task-based fMRI, and DTI optimized for structural and functional connectome analysis) on all eligible IADC participants, as well as amyloid and/or tau PET on 225 IADC participants. Participants in preclinical or early symptomatic phases (e.g., subjective cognitive decline (SCD) or with mild cognitive impairment (MCI)), late-onset AD, and individuals from families with mutations causal for dementias will be prioritized. Imaging-pathologic correlation when available will improve the understanding of early structural, functional, and molecular changes observed in vivo and may help identify novel therapeutic targets. Cross-modality image analyses and results of imaging genetics studies with ADNI, DIAN, and other partners will contribute to advances in early detection, mechanistic understanding, and optimized use of imaging as a dynamic biomarker for the study of therapeutic effects. Acquiring standardized state-of-the-art MRI and PET data for use by many investigators will increase research productivity and facilitate the optimized quantitative analyses. Close integration with other cores will further allow the IADC to expand on these analyses by relating imaging biomarkers to neuropsychological measures, neuropathologic samples, genetic and other ?omics markers. The NIC will continue to foster and support advanced imaging research through local, regional, and national/international collaborations. The IADC NIC will help advance AD imaging research to meet the goal of effective disease prevention and treatment within the next 10 years.